The long term objective of the project is to investigate cellular immune responses to Trichomonas vaginalis. The specific aims of this project are: 1) determine the local inflammatory and T cell responses to trichomonads; 2) determine the effects of parasites and primed T cells on macrophages; 3) examine the induction and mechanism of parasite killing by activated macrophages. T. vaginalis occurs as a sexually transmitted infection in humans resulting in vaginitis and cervicitis in women, is widespread in the U.S., and has been linked to low-birth weight, premature deliveries. Immunity to T. vaginalis is poorly understood and susceptibility of infected patients to re-infection implies that infection-induced immunity is not protective. Antibody responses are often demonstrated in infected women but the induction pathways are not understood and the basis of cellular immunity is unknown. After intravaginal inoculation of T. vaginalis with (or without) hormonal manipulation (estradiol) the local inflammatory and leukocyte population/phenotype changes will be investigated. Leukocyte surface makers, antigen-driven lymphocyte proliferation in vitro, histological determination of infiltrating leukocytes and activation states of macrophages of the reproductive tissues will be used to define the local immune response to T vaginalis. The direct effects of T. vaginalis on macrophage activation and cytokine expression will be determined by exposure of primary murine macrophages and macrophage lines to parasites followed by assay of oxygen and nitrogen intermediate, and, assay of cytokine mRNA and protein levels. The mechanisms of macrophage killing of T. vaginalis will be determined by exposure of parasites to macrophages activated with and without known inhibitors followed by parasite viability assays. These studies should identify patterns of T cell/macrophage priming and activations after vaginal exposure to T. vaginalis and some of the cellular immune pathways resulting in parasite killing.